The stability and targeting efficiency of nanoparticles (NPs) are the two most important issues for their applications to drug delivery and diagnostic imaging. Coating materials are needed to render NPs both stable and multi-functional to address these two issues. Polyethylene glycol (PEG) is the material most commonly used to modify NPs for stabilization purposes due to its resistance to nonspecific protein adsorption (or nonfouling properties). However, PEG is susceptible to oxidative damage and loss of function in biological media, which limits its long-term applications. Besides their stability in complex media, the stability of NPs themselves is another important issue that is often overlooked. NPs need to remain intact throughout any necessary manufacturing processes such as centrifugation or lyophilization. To maintain the stability of NPs, including those coated with PEG, several measures must be used such as low-speed ultrafiltration and addition of cryoprotectants prior to freeze-drying. For targeting drug delivery, bio-recognition elements (e.g., targeting ligands) often need to be immobilized onto NP surfaces. There is only one functional group potentially available at the end of a long PEG chain (e.g., 2-5 kDa) to which to conjugate biomolecules. In addition, unreacted functional groups can cause non-specific binding, particularly in complex media such as blood plasma and serum. With all current NP coating materials, one will have to compromise between excellent stability and multi-functionality.
Despite the advances in the development of NP coating materials, a need exists for a single material or coating platform that can accommodate both NP ultra-stability and multi-functionality.